rs34089864

chr11-116790052-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001371904.1(APOA5):c.*76C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,504,408 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.038 (185 hom., cov: 34)
  • Exomes 𝑓: 0.027 (1251 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-116790052-G-A is Benign according to our data. Variant chr11-116790052-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA5	NM_001371904.1	c.*76C>T		3_prime_UTR_variant	3/3	ENST00000227665.9
APOA5	NM_001166598.2	c.*76C>T		3_prime_UTR_variant	4/4
APOA5	NM_052968.5	c.*76C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA5	ENST00000227665.9	c.*76C>T		3_prime_UTR_variant	3/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2	c.*76C>T		3_prime_UTR_variant	4/4	1		P1
APOA5	ENST00000542499.5	c.*76C>T		3_prime_UTR_variant	4/4	5		P1
APOA5	ENST00000673688.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5734 AN: 152174 Hom.: 182 Cov.: 34

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0269 AC: 36431 AN: 1352116 Hom.: 1251 Cov.: 24 AF XY: 0.0283 AC XY: 18986 AN XY: 671854

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0302

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.0616

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome AF: 0.0377 AC: 5747 AN: 152292 Hom.: 185 Cov.: 34 AF XY: 0.0412 AC XY: 3071 AN XY: 74466

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0257 Hom.: 15

Bravo AF: 0.0362

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34089864; hg19: chr11-116660768; COSMIC: COSV57064776; COSMIC: COSV57064776;